This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Overview: Neurodegenerative diseases (ND) are generally associated with structural and functional brain abnormalities, including brain tissue loss and reduced cerebral blood flow. However, accurate detection of tissue loss and abnormal blood flow remains a challenge for MRI. Limited signal and contrast to noise ratios are major obstacles to measure subtle brain abnormalities with high precision. In addition, the complexity of neurodegeneration, including structural, functional, and metabolic abnormalities requires a multivariate imaging approach. The overall goal of this component of the Resource is to develop new methods of structural and perfusion MRI that provide improved signal and contrast to noise, resolution as well as sensitivity, in order to capture reliably and accurately brain alterations in ND. The Acquisition Core consists of three complementary projects. Here is the progress report of Project 1: Quantitative structural and dynamic perfusion imaging, which is directed by Dr. Schuff. Specific Aim1: Development of Multi-acquisition Variable T1-weighted Imaging (VTI) for Resolving Voxel Compartmentation and Enhancing Resolution: Resolution limits of MRI and the corresponding partial volume problem constrain precise measurements of structural alterations. Utilizing the different T1 values of brain tissue, we aim to overcome partial volume effects in structural MRI by developing multi-acquisition variable T1-weighted imaging (VTI) from which voxel compartmentation can be derived. Our efforts for VTI are specifically tailored toward precise measurements of cortical thinning and gray matter loss to enhance sensitivity for detection of diseases. Specific Aim 2: Development of Quantitative Evaluations of Cerebral Blood flow and Water Uptake into the Brain: While arterial spin labeling (ASL) in combination with volumetric (3D) gradient-and-spin-echo (GRASE) acquisitions have improved sensitivity to measure cerebral blood flow (CBF), quantification of CBF remains a challenge. Furthermore, local susceptibility effects resulting in geometrical and signal distortions at high magnetic fields can compromise measurement precision. Our efforts specifically aim at improved modeling of ASL signal dynamics to quantify cerebral blood flow and water uptake into the brain and correction of ASL signal distortions. We also aim at developing easy-to-use software for ASL image processing.